A blockage of portal vein can happen due to various
reasons in some children and can lead to portal hypertension and bleeding from
the upper gastrointestinal tract, and
enlargement of spleen. Upper gastrointestinal bleeding may not manifest any
symptoms but still lead to death and disability. In children,
this illness may result in repeated
hospitalization, absence from
school and emotional difficulties. Treatment
options include bypass surgery that bypasses the blocked area (to re-establish
the blood flow) and normally this means connecting
the superior mesenteric
and left intrahepatic portal veins using a vein graft.
A deceased or
cadaver donor vein graft or a liver transplant would mean life-long
anti-rejection drugs and were options that were not considered.
In this new procedure, the
research team bio-engineered a vein for the girl using the following technique
Initially, a 9-cm vein section or graft was obtained from a
30-year old organ donor and the cells from the vein were removed using buffer
and enzyme solutions over a period of 12 days.
The vein graft was then
treated with antibiotics and a sample piece was tested for the occurrence of
nuclei and HLA antigens.
Next, endothelial and smooth muscle cells were
prepared from the girl's bone marrow and placed in the vein graft for giving it
a new layer of cells that would not work as antigens.
After 2 weeks, endothelial
and smooth muscle cells were found in the lumen and walls of the vein graft
Once the vein was ready,
it was used to overcome the blockage by a surgical procedure.
A close follow up was done
to see if the graft functioned or if it got re-stenosed. This was done using
computerized angiography. To prevent the graft getting clotted, daily aspirin
(75 mg) was used for 6 months post-surgery.
The bypass graft
instantly provided the patient an efficient blood supply
of 25-30 cm/s in the portal vein and 40 mL/s in the artery. Following a revised
procedure a year later, the portal blood flow resulted in significant improvement
in the patient's physical and mental development and ability.
One year after surgery, the patient had a 6 cm
height (137 cm to 143 cm) and 5 kg weight increase (30 kg to 35 kg).
Though no mental cognition assessment was conducted, the patient's parents
described improvement in physical activity (2-3 km walks, simple gymnastics),
speech and focus in school.
This study has given
encouraging initial results and shown how stem cells may be used in future for
bioengineering vein grafts and provides hope to patients especially in
difficult situations as it was in this 10-year old girl.
Transplantation of an
allogeneic vein bioengineered with autologous stem cells: a proof-of-concept
study; Michael Olausson et al; The Lancet 2012